C. Herdeis, B. Kelm / Tetrahedron 59 (2003) 217–229
227
(COO2), 182.6 (COO2). MS (70 eV), m/z (%): 161 (0)
[Mþ], 144 (4) [Mþ2H2O], 99 (6), 98 (100), 70 (3), 55 (69).
3.1.29. (2S,3R)-3-Phenyl-glutamic acid (16e). To a
solution of 15e (2.00 g, 5.60 mmol) in EtOAc/methanol
(2þ1) (120 ml) was added palladium on charcoal. This
suspension was stirred for 4 h under hydrogen (4 bar). The
catalyst was removed by filtration and the mixture was
concentrated in vacuo to give an oily colourless residue.
This residue was treated with diethyl ether to give 16e as
colourless crystals. Yield 0.79 g (63%). Mp 1978C.
[a]2D0¼þ16.7 (c¼0.60, 6 M HCl); (lit:2c mp 158.0–
158.68C. [a]2D0¼þ16.7 (c¼1.36, 6N HCl). lit:2k
[a]2D0¼þ19.1 (c¼0.81, 6 M DCl)). C11H13NO4 (223.23):
calcd C 59.19, H 5.87, N 6.27; found C 57.91, H 6.08, N
5.77. IR (KBr): n (cm21)¼3150 (NH), 2940 (C–H), 2620–
2500, 1700 (COOH), 1620 (COO2), 1500 (C–H), 1410
(COO2). 1H NMR (DMSO-d6): d¼2.31 (dd, 1H, Jgem¼16.8
Hz, J4a–3¼6.4 Hz, H-4a), 2.72 (dd, 1H, Jgem¼16.5 Hz,
J4b–3¼9.5 Hz, H-4b), 3.64 (dt, 1H, J3–4a,6.4 Hz,
J3–4b,9.5 Hz, H-3), 4.08 (s, 1H, H-2), 7.21–7.45 (m, 5H,
3.1.27. (2S,3S)-3-Ethyl-glutamic acid (16b). To a solution
of 15b (0.50 g, 1.62 mmol) in EtOAc/methanol (1þ5)
(100 ml) was added palladium on charcoal. This suspension
was stirred for 6 h under hydrogen (4 bar). The catalyst was
removed by filtration and the mixture was concentrated in
vacuo to give a solid colourless residue. This residue was
treated diethyl ether to give 16b as colourless crystals. Yield
0.18 g (62%). Mp 1398C. [a]2D0¼þ49.3 (c¼0.78, 6 M HCl).
C7H13NO4 (175.18): calcd C 47.99, H 7.48, N 8.00; found C
46.12, H 7.04, N 7.66. IR (KBr): n (cm21)¼3050 (NH),
2970, 2940, 2880 (C–H), 2620–2500 (COOH), 1700
(COO2), 1485 (C–H), 1420 (COO2). 1H NMR (D2O):
d¼0.81 (t, 3H, J¼7.3 Hz, CH3), 1.26 (dq, 1H, J¼7.3 Hz,
JCH2-3¼7.0 Hz, CH2), 1.32 (dq, 1H, J¼7.3 Hz, JCH2-3
¼
7.0 Hz, CH2), 2.13–2.29 (m, 1H, H-3), 2.31 (dd, 1H,
Jgem¼16.5 Hz, J4b–3¼6.4 Hz, H-4b), 2.43 (dd, 1H,
1
aryl), 8.15 (s,,1H, N–H), 12.5 (s,,2H, carboxylate). H
Jgem¼16.5 Hz, J4a–3¼6.4 Hz, H-4a), 3.75 (d, 1H, J2–3
¼
NMR (D2O/NaOD): d¼2.53–2.69 (m, 2H, H-4), 3.21–3.56
(m, 2H, H-2 and H-3), 7.19–7.38 (m, 5H, aryl). 13C NMR
(D2O/NaOD): d¼39.14 (C-4), 47.65 (C-3), 62.26 (C-2),
127.1, 128.6, 128.8, 141.6 (6£C, aryl), 181.5 (COO2),
181.7 (COO2). MS (70 eV), m/z (%): 223 (0) [Mþ], 205
(25) [Mþ2H2O], 162 (16), 161 (13), 160 (100), 118 (10),
117 (73), 115 (20), 104 (63), 103 (13).
3.4 Hz, H-2). 13C NMR (D2O): d¼11.19 (CH3), 22.84
(CH2), 35.27 (C-4), 37.86 (C-3), 56.80 (C-2), 173.6
(COOH), 177.4 (COOH). MS (70 eV), m/z (%): 175 (0)
[Mþ], 157 (3) [Mþ2H2O], 113 (7), 112 (100), 84 (2), 83 (3),
69 (50).
3.1.28. (2S,3S)-3-(1-Butyl)-glutamic acid (16c). To a
solution of 15c (1.00 g, 2.96 mmol) in EtOAc/methanol
(1þ5) (100 ml) was added palladium on charcoal. This
suspension was stirred for 5 h under hydrogen (4 bar). The
catalyst was removed by filtration. The mixture was
concentrated in vacuo to give a solid colourless residue.
This residue was treated diethyl ether to give 16c as
colourless crystals. Yield 0.52 g (75%). Mp 122–1238C.
[a]2D0¼þ7.90 (c¼0.42, methanol). C9H17NO4 (203.24):
calcd C 53.19, H 8.43, N 6.89; found C 52.34, H 8.03, N
6.71. IR (KBr): n (cm21)¼3240 (NH), 2950, 2930, 2860
(C–H), 2620–2500 (COOH), 1710, 1680 (COO2), 1520,
1500 (C–H), 1440 (COO2). 1H NMR (CD3OD, 278C):
d¼0.98 (t, 3H, J¼6.7 Hz, CH3), 1.37–1.48 (m, 4H,
2£CH2), 1.51–1.57 (m, 2H, 1£CH2), 2.45–2.50 (m, 3H,
H-4b and H-3), 2.70 (dd, 1H, Jgem¼18.2 Hz, J4a–3¼8.0 Hz,
H-4a), 3.79 (d, 1H, J2–3¼3.2 Hz, H-2). 1H NMR (CD3OD,
508C): d¼0.97 (t, 3H, J¼6.8 Hz, CH3), 1.37–1.50 (m, 4H,
2£CH2), 1.51–1.58 (m, 2H, 1£CH2), 2.41–2.51 (m, 3H,
H-4b and H-3), 2.71 (dd, 1H, Jgem¼18.3 Hz, J4a–3¼6.9 Hz,
H-4a), 3.79 (d, 1H, J2–3¼3.3 Hz, H-2). 1H NMR
(D2O/NaOD, 278C): d¼0.86 (t, 3H, J¼6.7 Hz, CH3),
1.27–1.32 (m, 6H, 3£CH2), 1.96 (dd, 1H, Jgem¼13.1 Hz,
J4b–3¼10.6 Hz, H-4b), 2.05–2.13 (m, 1H, J3–4a,3.5 Hz,
J3–4b,10.6 Hz, J3–2,5.5 Hz, H-3), 2.16 (dd, 1H,
3.1.30. (2S,3R)-3-(4-Chlorophenyl)-glutamic acid (16f).
To a solution of 15f (2.00 g, 5.10 mmol) in EtOAc/methanol
(2þ1) (100 ml) was added palladium on charcoal. After the
suspension was stirred for 3 h under hydrogen (4 bar), the
catalyst was removed by filtration and the organic phase was
concentrated in vacuo to give an oily colourless residue.
This residue was treated with diethyl ether to give 16f as
colourless crystals. Yield 0.92 g (70%). Mp 1978C.
[a]2D0¼þ60.9 (c¼0.14, 1 M HCl), [a]2D0¼þ129 (c¼0.07,
1 M NaOH); (lit:2i mp 194.7–194.98C.2i [a]2D0¼þ21.5
(c¼0.39, 1N NaOH)). C11H12ClNO4 (257.67): calcd C
51.28, H 4.69, N 5.44; found C 52.69, H 4.17, N 5.36. IR
(KBr): n (cm21)¼3350 (NH), 2940, 2870 (C–H), 2620–
2500, 1740 (COOH), 1650 (COO2), 1490 (C–H), 1430
(COO2). 1H NMR (DMSO-d6): d¼2.25 (dd, 1H, Jgem¼16.7
Hz, J4a–3¼7.1 Hz, H-4a), 2.62 (dd, 1H, Jgem¼16.9 Hz,
J4b–3¼9.4 Hz, H-4b), 3.56 (dt, 1H, J3–4a,7.1 Hz,
J3–4b,9.4 Hz, J3–2,5.8 Hz, H-3), 4.03 (d, 1H, J2–3
¼
5.8 Hz, H-2), 7.31–7.40 (m, 4H, aryl), 8.11 (s, 1H, N–H),
12.7 (s,,2H, carboxylate). 1H NMR (CD3OD): d¼2.33 (dd,
1H, Jgem¼17.1 Hz, J4a–3¼6.4 Hz, H-4a), 2.74 (dd, 1H,
Jgem¼17.1 Hz, J4b–3¼9.2 Hz, H-4b), 3.59 (dt, 1H,
J3–4a,6.4 Hz, J3–4b,9.2 Hz, J3–2,5.2 Hz, H-3), 4.11 (d,
1H, J2–3¼5.2 Hz, H-2), 7.20–7.28 (m, 4H, aryl). 13C NMR
(CD3OD): d¼38.16 (C-4), 43.97 (C-3), 63.31 (C-2), 128.7,
129.0, 133.1, 141.5 (6£C, aryl), 173.6 (COOH), 178.3
(COOH). MS (70 eV), m/z (%): 257 (0) [Mþ], 241 (10), 239
(36), 196 (55), 195 (14), 194 (100), 151 (51), 140 (31), 139
(9), 138 (97), 117 (19), 116 (28), 115 (21), 103 (29).
Jgem¼13.3 Hz, J4a–3¼3.5 Hz, H-4a), 3.29 (d, 1H, J2–3
¼
4.2 Hz, H-2). 1H NMR (D2O/NaOD, 508C): d¼1.12 (t, 3H,
J¼6.6 Hz, CH3), 1.50–1.60 (m, 6H, 3£CH2), 2.23 (dd, 1H,
Jgem¼13.4 Hz, J4b–3¼10.3 Hz, H-4b), 2.30–2.38 (m, 1H,
J3–4a,3.5 Hz, J3–4b,10.3 Hz, J3–2,4.4 Hz, H-3), 2.43
(dd, 1H, Jgem¼13.4 Hz, J4a–3¼3.5 Hz, H-4a), 3.53 (d, 1H,
J2–3¼4.4 Hz, H-2). 13C NMR (D2O/NaOD): d¼13.75
(CH3, butyl), 22.46 (CH2, butyl), 28.75 (CH2, butyl),
30.47 (CH2, butyl), 38.94 (C-4), 39.83 (C-3), 57.93 (C-2),
182.6 (COO2), 182.8 (COO2). MS (70 eV), m/z (%): 203
(0) [Mþ], 185 (2) [Mþ2H2O], 141 (9), 140 (100), 98 (3), 97
(11).
3.1.31. (2S,3R)-3-(1-Naphthyl)-glutamic acid (16h). To a
solution of 15h/16h [ratio 10:1] (0.40 g, ,0.98 mmol) in
EtOAc/methanol (1þ1) (50 ml) was added palladium on
charcoal. This suspension was stirred for 8 h under
hydrogen (4 bar). The catalyst was removed by filtration
and the mixture was concentrated in vacuo to give an oily